ROLE OF CGMP-KINASE-II IN THE CONTROL OF RENIN SECRETION AND RENIN EXPRESSION

To investigate the roles of the cGMP-dependent protein kinases (cGKs) in the control of the renin system, we studied the regulation of renin in cGKI- or cGKII-deficient mice in vivo and in vitro. Renal renin mR NA levels both under stimulatory (low-salt diet plus ramipril) and inh ibitory (high-salt diet) conditions were not different between wildtyp e and cGKI-/- mice, but were significantly elevated in cGKII-/- mice u nder all experimental conditions. In primary cultures of renal juxtagl omerular cells (JG) established from wild-type, cGKI-/-, and cGKII-/- mice, the adenylate cyclase activator forskolin stimulated renin secre tion similarly in all genotypes tested. 8-bromo-cGMP attenuated basal and forskolin-stimulated renin secretion in cultures from wild-type an d cGKI-/-, but had no effect in cells isolated from cGKII-/- mice. Act ivation of cGKs by 8-bromo-cGMP decreased renin secretion from the iso lated perfused rat kidney, independent of prestimulation by beta-adren oreceptor activation, macula densa inhibition, reduced perfusion press ure, or by a nominally calcium-free perfusate. Taken together, these f indings suggest that activation of cGKII has a general inhibitory effe ct on renin secretion from renal JG cells.